Pemetrexed in second-line treatment of non-small-cell lung cancer

According to the updated 2004 guidelines of the American Society of Clinical Oncology (ASCO) on the treatment of advanced non-small-cell lung cancer (NSCLC), docetaxel (Taxotere) can be considered the standard second-line chemotherapy in patients relapsing after frontline therapy. This was based on two phase III trials (TAX 317 and TAX 320) that demonstrated the superiority of docetaxel at 75 mg/m2 in the parameters of survival, quality of life, and disease/symptom control when compared to best supportive care or alternative single-agent chemotherapy. The response rate was approximately 60%, with a median survival time of 7 months and a 1-year survival rate of 30%. Despite the activity demonstrated, this schedule showed an important toxicity profile, with grade 3/4 neutropenia and febrile neutropenia occurring in 70% and 11% of patients, respectively. However, the results obtained by these studies stimulated research interest in new drugs for this disease setting. Pemetrexed (Alimta), a new multitargeted antifolate, has achieved promising results in NSCLC treatment, as a single agent or in combination with other drugs. In the second-line setting, a large phase II study demonstrated good activity of pemetrexed, with an acceptable toxicity profile. This led to a phase III registration trial that compared pemetrexed at 500 mg/m2 to the standard docetaxel dose of 75 mg/m2. While results from this trial demonstrated a similar efficacy of the two regimens in response rate and survival, pemetrexed achieved a better safety profile. These results support the use of pemetrexed as a new option in the second-line treatment of NSCLC.